“Interrogating the epigenetic mechanisms of chemotherapy resistance in cancers”
Tuğba Bağcı Önder, Ph.D.
Koç University, School of Medicine
Date-Time : Wednesday, November 03, 2021 at 15:30
Host : Doç. Dr. Işık Yuluğ
***This is an online event. To obtain Zoom link and password, please contact to the department.
Dr. Tuğba Bağcı Önder graduated from the Department of Molecular Biology and Genetics, Bilkent University in 2002. She then earned her Ph.D. degree in Neuroscience at Sackler School of Graduate Biomedical Sciences at Tufts University in 2008.
She pursued her postdoctoral work at Harvard Medical School, Massachusetts General Hospital on the development of tumor-specific pro-apoptotic therapies in animal models of brain cancer.
In 2012, she joined Koç University School of Medicine and established the Brain Cancer Research and Therapy Laboratory. Her research group is currently working on the understanding of epigenetic regulation of cell death, therapy resistance and progression of cancers.
Her work is supported by FP7 Programme-Marie Curie Career Integration Grant, TÜBİTAK, and the American Hospital.
Dr. Bağcı Önder is also a recipient of Barbara Talamo Trainee (2008), UNESCO-L’oreal Women in Science (2013) and BAGEP (2014) awards.
A mechanism of therapy resistance is transcriptional dysregulation of cell death and survival-related genes. Changes in the epigenome are stably inherited through cell divisions and are thought to play a role in acquired therapy resistance. Epigenetic modifications occur on chromatin and consist mainly of DNA methylation, histone acetylation and methylation. These modifications regulate gene expression by influencing the packaging of chromatin and accessibility of transcription machinery to specific genes. A number of protein complexes write, read and erase chromatin modifications and the role of these complexes in tumor biology is starting to be heavily investigated. These complexes can be broadly categorized as DNA methyl-transferases (DNMTs), histone acetyl-transferases (HATs), histone deacetylases (HDACs), histone methyl-transferases (HMTs) and histone demethylases (HDMs)
In order to decipher the relationship between therapy response and epigenetics, we undertake loss-of-function approach and interrogate the roles of chromatin modifying proteins with functional screens. These screens are based on genetic or chemical ablation of protein functions. In the first one, we use shRNA or CRISPR/Cas9-based libraries, in the second one we use chemical probes in order to discover novel molecular mechanisms to overcome therapy resistance. In our studies, we utilize next generation sequencing to profile and map the differences between drug-sensitive and drug-resistant populations of cancer cells. In this seminar, I will talk about our current approaches and highlight the roles of our recently identified molecular mechanisms.